Abstract
AbstractDevelopment and engineering of protein crystals regarding mechanical stability and crystallizability occurs on a small scale. Later in the process chain of industrial production however, filtration properties are important to separate the crystals from mother liquor. Many protein crystals are sensitive to mechanical stress which is why it is important to know the filtration behavior early on. In this study, we analyze settling and filtration behavior of isometric, rod‐like and needle shaped lysozyme and rod‐like alcohol dehydrogenase (ADH) crystals on a small scale using an optical analytical centrifuge. Needle shaped lysozyme and rod‐like ADH crystals show compressible material behavior. With the results from settling and filtration experiments, the flux density function is calculated and modeled which can be used to describe the whole settling and permeation process in dependency of the solids volume fraction. This is also an issue for simulations of industrial processes.
Highlights
The improvement of bulk protein crystallization for purification or formulation is subject of current research
This study considers three different lysozyme crystal systems and the commercially not available crystal system alcohol dehydrogenase (ADH) from L. brevis
The mass specific filtration resistance obtained from permeation experiments in the centrifuge are shown in Figure 5 left and corresponding height specific resistances are shown on the right-hand side of Figure 5
Summary
The improvement of bulk protein crystallization for purification or formulation is subject of current research. Crystalline proteins are advantageous compared to dissolved or amorphous solids because of their extended shelf life or modified drug release properties.[1,2] The implementation of a crystallization step in the downstream process chain for protein purification and formulation is discussed in literature by Hubbuch et al.[3] and Hekmat et al.[4] In recent research either the proteins were modified to improve or enable crystallization, or the crystals itself were altered to enhance mechanical stability.[5,6,7] Nowotny et al.[5] and Hermann et al.[6] identified crucial amino acids for crystallization in the sequence of the protein alcohol dehydrogenase from Lactobacillus brevis in a rational crystal engineering approach using a molecular dynamics model. In numerical simulations of settling or filtration processes, the flux density function combined with the compressible yield stress are useful input parameters to model the whole separation process
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